William A Beresford MA, D Phil ©
Professor of Anatomy
Anatomy Department, West Virginia University, Morgantown, USA
Chapter 21 SKIN
Skin/integument covers the body and serves many functions. It consists of a
thick, protective, cornified, stratified squamous epithelium (epidermis),
on a firm, dense CT lamina propria (dermis), and has special
appendages, hair and nails, and accessory glands, sweat,
sebaceous, and mammary glands (Chapter 29.D).
A EPIDERMIS (epithelium)
l Stratum corneum of keratinized cells (outermost).
2 Stratum lucidum, a thin pale layer of keratin seen when the stratum
corneum is very thick.
3 Stratum granulosum of cells with basophilic granules.
4 Stratum spinosum of keratinocytes/prickle epithelial cells.
5 Stratum germinativum, bordering on the BL.
2 Cytological details of the layers
l Stratum germinativum/basale
2 Stratum spinosum
- (a) Keratinocyte precursor cells, cuboidal or columnar in form, lie
on a BL.
- (b) Cells project down many small basal processes.
- (c) The whole underside of the epithelium is indented by CT dermal
papillae for effective attachment, nutrition, and sensation.
- (d) Cells proliferate to replace lost surface cells.
3 Strata granulosum and corneum.
- (a) Keratinocytes/prickle cells
... (i) Principal cell kind; ectodermal in origin; move upwards in the layer
and continue to proliferate, despite the many desmosomes holding them together
(which, with processing shrinkage, lead to the cells' spiny, prickly
... (ii) Cytoplasm is rich in keratin filaments, bundled into tonofilaments
and increasing in number towards the keratin layer, and formed from prekeratin
- (b) Melanocytes
... (i) Ectodermal; but migrated
neural crest cells.
... (ii) Constitute l in 4 to l in l0 of basal epithelial cells.
... (iii) Deficient in tonofilaments and desmosomes.
... (iv) Synthesize melanin and transfer it via their long dendritic
processes to neighbouring keratinocytes.
... (v) EM shows that the Golgi apparatus participates in forming the
... (vi) Melanin is formed from tyrosine by the enzyme tyrosinase. Cells with
melanin-forming ability can be revealed in a section by treating it with
dihydroxphenylalanine (DOPA), which is oxidized to melanin.
... (vii) Albinos have an inborn error of metabolism, making them unable
to synthesize melanin in the skin and eye.
... (viii) UV light causes greater melanin formation and a thickening
of the keratin layer. Pituitary and adrenal hormones also
increase pigmentation, which is a useful sign for diagnosis.
- (c) Langerhans cells are poorly phagocytic, marrow-derived,
specialized macrophages, with long dendrites. They are antigen-presenting cells,
accessory to T-cell immunity.
- (d) Merkel cells are sensory cells with vesicles and a
polylobulated nucleus. They attach to disc-shaped endings of some of the
axons that penetrate the epithelium.
(a) Stratum granulosum cells form
a kerato-hyaline matrix from their basophil granules, binding together
packed tonofilaments within the cells to convert the cells to soft
keratin. Other organelles and the nucleus vanish, while the plasmalemma
thickens and toughens, to build a cornified envelope.
(b) Flattened, dead, keratinized, surface cells desquamate.
(c) Only with EM is keratin seen to be cellular. In the usual HE
preparation it is eosinophilic, and often splits and breaks.
(d) Epidermis is thrown up into ridges - cristae cutis - on the palmar and
plantar surfaces of the hands and feet: the basis of finger and palm prints.
(e) At the top of the ridges, spiralling holes open through the
keratin to let out the sweat.
(f) Keratin layer may be very thick, for instance on the soles and
palms. Such thick skin is hairless, and lacks sebaceous glands.
(g) The molecular epidermis:- Filaggrin is the protein of keratohyaline granules, and aggregates
'keratinocyte' keratins Nos. 5/14. These acidic-basic combinations of
keratins (numbered indirectly according to Mr) are characteristic for
particular classes of epithelia, e.g., simple versus squamous, and help
in interpreting pathological changes. Directly under the plasmalemma is a complex
of proteins that are made dense and insoluble - to constitute the "envelope" -
by transglutaminase-mediated cross-linking. One protein of the cornified cell
envelope is involucrin. Ceramide and other extracellular lipids surround the
envelope to boost the barrier function.
B DERMIS (Corium)
l Divided into layers: papillary, fine-textured CT adjacent to the
epidermis, and a deeper reticular layer.
2 Reticular layer is thick collagenous CT of a variable
thickness, not always related to that of the overlying epidermis.
3 Elastic fibres of the dermis give skin its elasticity, but cause
wounds to gape. Ruptured dermis often heals as a white line visible through
the epidermis, e.g., a mother's stretch marks.
4 Has the usual cells of CT - fibroblasts, macrophages and other
defensive cells, and sometimes pigment-bearing chromatophores/dermal
5 Smooth muscle of arrectores pilorum, nipples and scrotal dartos,
and skeletal muscle in the scalp and face, are attached in the dermis.
6 Blood vessels are derived from arterial plexuses: a deep cutaneous
plexus/rete, and a subpapillary plexus sending capillary loops up into
dermal papillae. Lymphatics accompany blood vessels. Blood flow is
varied greatly by shunts through glomi (coiled arteriovenous anastomoses),
and by the constriction or relaxation of arterioles.
7 Nervous receptors (Chapter 12.B), with sensory nerve fibres
are present; and autonomic nerve fibres:
.. vasomotor to vascular smooth muscle,
.. pilomotor to hair arrector muscles,
.. sudomotor to sweat glands.
8 Hair follicles and glands lie mostly in the dermis.
C SWEAT GLANDS (Glandulae sudoriparae)
l Single coiled tubules, lined by simple cuboidal light and dark cells;
distributed over the body except for the lips, glans penis and inner prepuce.
2 Secretory part lies in the lower dermis, or subcutaneously in the
hypodermis/superficial fascia. One tubule is cut through many times in one
3 The secretion, mainly water and electrolytes plus some lipids, is
led to the epidermis through a duct, lined by stratified cuboidal
epithelium, then through the living/Malpighian layer and a spiralling hole in the
keratin. The gland's chloride channel is one that is impaired in cystic
4 Myoepithelial cells are seen within the basal lamina of the
secretory tubule. Their contraction is under autonomic control.
5 The larger variety of gland seen in the axillary, perianal and
perigenitalial regions is termed apocrine, in contrast to the eccrine
glands in the majority. Apocrine glands become active with pubertal
development of the ambosexual hair, and may be related to animals' scent
6 The ceruminous glands of the external auditory meatus seem to be
enlarged sweat glands, producing a secretion of pigmented lipids.
D SEBACEOUS GLANDS
l Pear-shaped, simple, branched alveolar, with large cells, usually looking
vacuolated because their fatty content is dissolved out.
2 Several glands are clustered by the side of a hair follicle, into which
they discharge the secretion - sebum. Their short duct is lined by
stratified squamous epithelium.
3 Sebum, formed in a holocrine manner by the total breakdown of the
cells, may lubricate the hair shaft, protect the skin from drying and
moisture, and be bacteriostatic.
4 Lie independently of hairs on the labia minora, glans penis, in the oral
mucosa by the red margin of the lips, and as the Meibomian glands
of the eyelid. They are absent from the palms and soles.
l Varieties and sites
1 Lanugo - fine, fetal, hairy covering, shed at birth.
2 Replaced by the vellus - fine body hairs.
3 Scalp, eyebrow and eyelash hairs are thicker.
4 Ambosexual hair - pubic and axillary.
5 Masculine hair - face (beard), chest and extremities.
2 Hair development
l Hair is a hard keratin derivative of the epithelium of a hair
2 In development, an epithelial bud grows down from the young
epidermis; a vascular CT dermal papilla invaginates the bud; in the bud a
germinal matrix develops, forming the special keratin; and side buds
form sebaceous glands.
3 Hair shaft comprises:
4 Hair follicle
- (a) Medulla, as the central core of soft keratin and sometimes air
spaces. The medulla may be absent.
- (b) Cortex of closely packed, elongated, hard-keratinized cells,
formed without any intermediary kerato-hyaline granules developing. Melanin
and other pigments may be incorporated in the cells during keratinization.
- (c) Cuticle - outermost coat of shingled/imbricated cells, with their
free edges projecting upwards.
- (a) Outer CT sheath and inner basal lamina (hyaline membrane).
- (b) Vascular papilla lies directly under the synthesizing
epithelial area, responsible for the upward growth of the hair and its inner
- (c) External root sheath is a continuation of the epidermal
living layer, expanding to form the basal hair bulb.
- (d) Internal root sheath forms a cuticle layer from which the
other cuticle, on the hair, can separate at the level of entry of the
sebaceous gland's duct. The internal root sheath thus comprises: (a) innermost
cuticle cells, (b) Huxley's layer of cells with trichohyaline granules,
(c) Henle's single, outer layer of clear cells.
- (e) Epidermal germinal matrix, above the papilla, forms the hair's
cuticle, cortex and medulla. NB - the appearance of cross-sections varies with
the level in the hair follicle at which they are taken.
- (f) Arrector pili of smooth muscle fastens the lower hair bulb's
CT sheath to the upper dermis nearby.
5 Epithelial replacement and hair growth are cyclical, not constant
activities. The hair stops growing, via a relatively short catagen
period of regression or involution, to enter a long non-growing telogen
phase of being a club hair, which eventually falls out. It is replaced
during an anagen/growth phase by a new hair from the reactivated deep
region of the follicle.
3 Pilomotor activity
Hairs are raised from their relaxed, inclined attitude by contraction of their
arrectores pilorum muscles in response to cold, so that more insulating
air is trapped near to the skin. Hairs also 'stand up' in fear and other
l The horny plate of hard beta keratin is synthesized by
2 the proximal, germinal, part of the nail bed.
3 The nail bed comprises the living layers of the epidermis,
ridged longitudinally, and lacking glands and follicles. Part
of its germinal region is seen by the naked eye as the
4 lunule, the pale half-moon area just distal to the eponychium
- an extension of the stratum corneum of the dorsal skin.
G SKIN FUNCTIONS
l Protection against water, bacteria, sunlight, mechanical forces,
dehydration, cold, etc.
2 Retaining body fluids, i.e., protection against dehydration.
3 Temperature regulation by: (a) varying peripheral blood flow, (b)
sweating, (c) hair elevation, and (d) insulation by adipose tissue under the
skin. (Note that heavy sweating defeats 2 above.)
4 Food storage and fat metabolism in the subcutaneous hypodermis.
5 Vitamin D formation by the action of ultraviolet light.
6 Sensory appreciation of the environment by nervous receptors:
7 Friction surface for motor tasks involving grasping, rubbing,
8 Display and communication: social, sexual, and diagnostic.
Many diseases distinctively affect the skin and its hair and nails.
The tract rhythmically expels spent air and takes in fresh through
conditioning passages, conducting it to the respiratory portion of the lungs,
where the walls of the air-filled chambers are thin enough to permit an
exchange of gases between blood and air. The respiratory movements
involve chemoreceptors, brain centres, the thoracic cage, and various muscles:
these structures belong, together with the respiratory tract, in the
respiratory system Powerpoint. The lungs also have important metabolic
functions not directly related to gas exchange, e.g., the activation of
circulating angiotensin I, and the inactivation of some other vasoactive agents.
A RESPIRATORY TRACT TO LUNGS
l Nasal cavity
l Divided by a hyaline-cartilage nasal septum in the midline.
2 Stratified squamous epithelium (hairy) of the nares changes to
3 a lining nasal mucosa of:
.. (a) pseudostratified, columnar, ciliated epithelium with
mucus-secreting goblet cells, on
.. (b) a loose lamina propria, with many leucocytes, blood vessels,
and mixed muco-serous glands.
4 Venous plexuses, to warm the air, underlie the epithelium.
5 Turbinate bones in the conchae support the mucosa.
6 A small part of the mucosa is olfactory, with a neuroepithelium
(Chapter l2.B.5.la) and Bowman's glands.
7 Paranasal air sinuses open off the main cavity.
8 The folded pharyngeal tonsil, covered by pseudostratified, columnar,
ciliated epithelium, lies posteriorly in the pharynx.
9 Nasal functions:
- (a) air-filtering, material trapped in mucus is swept by the cilia towards the pharynx,
- (b) air-warming,
- (c) air-humidifying,
- (d) olfaction,
- (e) sensitivity for nasal reflexes such as sneezing,
- (f) resonating the voice.
l Hollow chamber, whose walls are supported by cartilages, connected by
ligaments and membranes, and moved by skeletal muscles.
2 The extrinsic and intrinsic muscles move the larynx up and
under the epiglottis in swallowing, and move the cartilages and tense the
vocal cords during phonation and breathing.
3 The cartilages are hyaline tending to calcification, or
elastic for the epiglottis, cuneiforms, corniculates, and the apices
and vocal processes of the arytenoids.
4 Mucosa is mostly pseudostratified, columnar, ciliated epithelium
with goblet cells, on a loose lamina propria rich in elastic fibres, mucous
and mixed glands, leucocytes and sometimes lymphoid nodules.
5 Two constrictions occur: the false vocal cords/ventricular folds;
and the lower, true, cords. The true vocal chords are elastic ligaments
tensed by the adjacent vocalis muscle, and are covered with stratified squamous
epithelium. There are no glands in their lamina propria.
6 The epiglottis, too, has stratified squamous epithelium on its
exposed tip and upper surface.
l Flexible, extensible tube, with an always-patent lumen.
2 Mucosa as for the larynx, and the cilia sweep towards the pharynx,
but the elastic fibres run longitudinally as a layer between mucosa
3 Supporting C-shaped pieces of hyaline cartilage are incomplete on
their oesophageal side.
4 The gap in the C is crossed by trachealis smooth muscle and CT.
5 Outer adventitia is fibro-elastic CT.
The structure of the lungs reflects the way in which the air is moved:
l Bronchial tree serving the lungs
- (a) the lungs are covered by a slippery membrane and are enclosed in
another membrane, adherent to the inner chest wall, with a potential space between;
- (b) the lungs are stretched out against their considerable elasticity,
so that this space remains only a potential one;
- (c) the larger conducting tubes of the lung need firm cartilages in
their walls to prevent their collapsing during the inspiratory sucking in of air.
l Primary bronchi branch to form the
2 intrapulmonary lobar bronchi, branching to form segmental
bronchi, then lobular bronchioles. After about 9-l2 generations of
branching, bronchioles replace bronchi.
3 Terminal bronchioles lead to respiratory bronchioles, off
which open the respiratory exchange units, and not just at the end, but
along the bronchiole. [For efficiency, the branching, tubular architecture
of air conductance overlaps slightly the honeycomb architecture of gas
4 Bronchi resemble the trachea in structure, except that the
cartilage pieces in the wall have very irregular shapes, and the smooth
muscle forms a nearly complete layer - muscularis mucosae - between the
cartilages and the lumen.
5 Bronchioles are smaller than bronchi:
.. they have no cartilages;
.. their elastic fibres merge with those of the surrounding lung tissue;
.. the epithelium changes to simple, low ciliated columnar with a few goblet
.. no mucous glands are present in the lamina propria, where the smooth muscle
is relatively substantial.
6 Sharing the connective tissue of the branching bronchi are blood vessels,
nerves and lymphatic vessels, entering or leaving at the hilum or lung root.
7 Hilar structures include arteries (bronchial and pulmonary), veins,
lymphatics (from two systems), bronchi, lymph nodes, ganglia, nerves (to bronchial,
bronchiolar, and vascular smooth muscles; and sensory), and adipose
and other CT.
The carotid body-like glomus pulmonale in the pulmonary artery's adventitia
is of uncertain function.
2 Mucosa of the lower airway
3 Respiratory chambers
- Cell types in the epithelium:
- (a) ciliated columnar cells, with lysosomes and some microvilli;
- (b) mucus-secreting goblet cells;
- (c) basal 'undifferentiated' cells to replace the specialized kinds;
- (d) Clara's non-ciliated bronchiolar secretory cells with granules and GER;
- (e) neuroendocrine cells;
- (f) lymphocytes migrated from the lamina propria.
- A sheet of sticky mucus is moved by ciliary action over the mucosa to
catch and remove particles - the mucociliary escalator.
- The basal lamina typically is thick.
- Muco-serous mixed glands, where present in the lamina propria, are small,
compound tubular, and respond under nervous control to irritant stimuli, e.g.,
l Respiratory bronchiole has simple, low columnar or cuboidal
bronchiolar and ciliated cells; elastic fibres and smooth muscle support the
2 Opening out along the respiratory bronchiole are alveoli, whose
openings are ringed by smooth muscle.
3 At the end of the respiratory bronchiole are one or more long alveolar
4 Alveolar ducts can be viewed as being three to six atria,
vestibules, leading to alveolar sacs, made up of varying numbers of
Processing distortions in lung slides often make the atria and sacs hard
to make out.
5 One alveolus or cubicle shares an alveolar wall with the ones
adjacent and backing on to it. The wall is thus interalveolar and carries
the many capillaries, whose blood is to receive oxygen and give up
6 Angiotensin converting enzyme in pulmonary capillaries cleaves
angiotensin I to make it the potent angiotensin II.
4 Interalveolar wall
l Air side - continuous alveolar epithelium with:
.. (a) type I pneumocytes/squamous cells; and
.. (b) pneumocytes type II/septal or great alveolar cells, with
prominent lipid cytosomes/ multilamellar bodies in their cytoplasm.
2 Surfactant is a stabilizing fluid film of lipids (90%) and proteins
(10%), covering the epithelium and lowering surface tension. The principal
surface-active agent is the lipid, dipalmitoyl phosphatidylcholine (DPPC).
The type II cells synthesize this film, but also are the stem cell to replace
themselves and Type I cells. Cytosomes are stored surfactant.
3 Alveolar macrophages/dust cells lie free in the alveoli.
4 Alveolar epithelium lies on a basal lamina sometimes merging with,
and sometimes separated from, the
5 basal lamina of a blood capillary, on which lies an
6 unfenestrated endothelium on the blood side.
7 Where the two basal laminae are separated, the space - zona
diffusa - is taken by elastic and reticular fibres, fibroblasts, macrophages
and other CT cells.
8 The pulmonary blood-air barrier can therefore be as thin as 300 nm, and
has a very extensive area.
9 Communication between adjacent alveolar sacs is through holes in the wall -
l0 Basal laminae, fibres, and surfactant maintain the shape and patency of
alveoli during respiration.
5 Pleurae are fibro-elastic vascular membranes with mesothelial
coverings. From the visceral pleura, CT septa run in to subdivide the
lung into lobules and carry lymphatic and venous vessels.
C RESPIRATORY TRACT
l From an endodermal bulge on the foregut, which gives the trachea,
then two buds for the bronchi and lungs.
2 Continued budding and branching, and enclosure of the hollow
buds by mesenchyme, produce a system of cuboidal epithelium-lined
tubules with surrounding differentiating CT and vessels.
3 Early development thus is analogous to that of a compound exocrine gland,
until the later phase, when the pulmonary alveoli form. Inadequately developed
alveoli, with no surfactant, are a major hazard of premature birth.
4 Surfactant comprises lipids, and surfactant glycoproteins SP-A, -B, -C, & -D,
which variously cause the lamellar material to become a monolayer, enhance
the lowering of surface tension, stabilise the lipids, and modify host
5 For the development of glands and the lung, complex mesenchymal-epithelial
inductive (instructional) interactions occur, and recur during repair and
2 Respiratory protective mechanisms
- Secretion of entrapping mucus by goblet cells and mixed glands,
- which is swept pharynx-wards by the ciliary beating action.
- Solitary lymphoid nodules and tonsils, and their lymphocyte progeny, for
- Phagocytic alveolar macrophages/dust cells.
- Reflex coughing, sneezing, and constriction of bronchioles.
- Secretion of serous bacteriolytic materials, e.g., defensins and lysozyme.
- Upper airway recovers water and heat, preventing too much loss in the
Some protection is hazardous in that enzymes from WBCs can break down elastin;
and activated lung macrophages stimulate fibroblasts to lay down
movement-restricting collagen - an interstitial fibrosis.
Various defects in the arms and microtubules of cilia (primary ciliary
dyskinesia) can prevent proper clearance and cause recurrent lung infection.
Affected men are often infertile from an accompanying paralysis of sperm.